For immune response to oral pathogens is the result of a coordinated division of labor between the mucosal and central immune systems. While it is clear that these parts of the immune response are compartmentalized, there is surprisingly little information about the regulation of their interaction In fact, even the role of the mucosal immune system in controlling or preventing opportunistic pathogens in the mouth is poorly defined. We propose to perform a wide range of assays to determine specific defects in the immune response to oral pathogens in the context of HIV disease. We will examine both the systemic response as well as the in situ mucosal response to Candida albicans, Epstein Barr virus, and human papillomavirus, -three pathogens responsible for the most common opportunistic infections of the oral cavity in HIV-infected people: candidiasis, hairy leukoplakia, and oral warts. Our studies are unique in that they employ new and powerful technologies that can, for the first time, provide detailed information about the precise immunological response to these pathogens, measured either for cells in the blood (a measure of the systemic immune response) or for cells in the lesions themselves (as a measure of the local immune response). We hope to identify specific defects that correlate with the presence or progression of oral diseases even in the context of HAART. In a larger sense, these studies will provide the first detailed view of the coordination of the immune response at the level of the oral diseases even in the context of HAART. In a larger sense, these studies will provide the first detailed view of the coordination of the immune response at the level of the oral lesion, the topological and functional organization of the various immune cells that respond to the infection. These studies will significantly extend our knowledge of mucosal immunology in general.